Dose Escalation and Expansion Study of FLX475 Monotherapy and in Combination With Pembrolizumab

Phase 1/2 Dose-Escalation and Expansion Study of FLX475 Alone and in Combination With Pembrolizumab in Advanced Cancer

This clinical trial is a Phase 1/2, open-label, sequential-group, dose-escalation and cohort expansion study to determine the safety and preliminary anti-tumor activity of FLX475 as monotherapy and in combination with pembrolizumab.

The study will be conducted in 2 parts, a dose-escalation phase (Part 1) and a cohort expansion phase (Part 2). In Part 1 of the study, subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 as monotherapy or in combination with pembrolizumab. In Part 2 of the study, subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 as monotherapy or in combination with pembrolizumab.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Cancer
• Intervention / Treatment: Drug: FLX475; Drug: pembrolizumab (KEYTRUDA®)

• Study Type: Interventional
• Enrollment (Actual): 323
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Linear Clinical Research Limited
• Hong Kong
  • High West, Hong Kong
    • Queen Mary Hospital
  • High West, Hong Kong
    • Queen Mary Hospital - Lymphoma
  • Shatin, Hong Kong
    • Prince of Wales Hospital
• Korea, Republic of
  • Chungbuk, Korea, Republic of, 28644
    • Chungbuk National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 03080
    • Seoul National University
• Taiwan
  • Tainan, Taiwan, 70403
    • National Cheng Kung University Hospital
  • Tainan, Taiwan, 71004
    • Chi Mei Meidcal Center
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
• Thailand
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital
  • Bangkok, Thailand, 10330
    • King Chulaongkorn Memorial Hospital
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Los Angeles, California, United States, 90024
      • University of California, Los Angeles JCCC Clinical Research Unit
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown - Lombardi Comprehensive Cancer Center
  • Florida
    • Saint Petersburg, Florida, United States, 33709
      • Comprehensive Hematology and Oncology, LLC
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Winship Cancer Institute
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville Hospital/James Graham Brown Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • Quantum Santa Fe
  • New York
    • New York, New York, United States, 10032
      • New York Presbyterian Hospital-Columbia University Medical Center
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Carolina BioOncology Institute
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research Center
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented advanced or metastatic cancer ineligible for standard therapies with one of the following histologies

  • Dose Escalation: non-small cell lung cancer, head and neck squamous cell carcinoma, nasopharyngeal carcinoma, metastatic triple negative breast cancer, urothelial carcinoma, gastric cancer, esophageal carcinoma, cervical cancer, classical Hodgkin lymphoma
  • Dose Expansion: nasopharyngeal carcinoma, lymphoma, head and neck squamous cell carcinoma, cervical cancer, non-small cell lung cancer, triple-negative breast cancer
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• Evaluable disease at baseline (at least one measurable target lesion by imaging for expansion cohorts)
• Tumor available for biopsy

Exclusion Criteria:

• History of allergy or severe hypersensitivity to biologic agents
• History of Grade 3-4 immune-related adverse events leading to discontinuation of prior immuno-oncology treatment
• Active autoimmune disease or serious autoimmune disease within past 2 years requiring systemic therapy
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, (non-infectious) pneumonitis that required steroids, or symptoms of active pneumonitis
• Prior allogeneic hematopoietic stem cell transplant within 5 years, or prior allogeneic organ transplant
• Active graft-versus-host disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1a: Monotherapy Dose Escalation; Eligible subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 as monotherapy.	Drug: FLX475; tablet
Experimental: Part 1b: Combination Dose Escalation; Eligible subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 in combination with pembrolizumab.	Drug: FLX475; tablet; Drug: pembrolizumab (KEYTRUDA®); IV infusion
Experimental: Part 2a: Monotherapy Expansion Cohorts; Eligible subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 as monotherapy; additional subjects in each cohort may be enrolled in Stage 2.	Drug: FLX475; tablet
Experimental: Part 2b: Combination Expansion Cohorts; Eligible subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 in combination with pembrolizumab; additional subjects in each cohort may be enrolled in Stage 2.	Drug: FLX475; tablet; Drug: pembrolizumab (KEYTRUDA®); IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of FLX475 as a single agent and in combination with pembrolizumab measured by the incidence of adverse events, including dose-limiting toxicities and maximum tolerated dose	Approximately 18 weeks
Overall response rate in subjects treated with FLX475 as a single agent and in combination with pembrolizumab	Through study completion (approximately 2 years)

Collaborators and Investigators

• Sponsor: RAPT Therapeutics, Inc.
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: William Ho, MD, PhD, RAPT Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2018
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: September 14, 2018
• First Submitted That Met QC Criteria: September 14, 2018
• First Posted (Actual): September 17, 2018

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Breast Cancer; Urothelial Carcinoma; Lymphoma; Cervical Cancer; Non-small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma; Nasopharyngeal Carcinoma
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: FLX475-02; KEYNOTE-877 (Other Identifier: Merck Sharp & Dohme LLC); MK-3475-877 (Other Identifier: Merck Sharp & Dohme LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No